Increase of capsaicin-induced trigeminal Fos-like immunoreactivity by 5-HT(7) receptors.

Increase of capsaicin-induced trigeminal Fos-like immunoreactivity by 5-HT(7) receptors.
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5-HT(7)受体增加辣椒素诱导的三叉神经FOS样免疫反应性。

DOI:
10.1111/j.1526-4610.2011.02011.x
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发表时间:
2011-11
期刊:
影响因子:
5
通讯作者:
Terrón JA
Terrón JA
中科院分区:
医学3区
文献类型:
--
作者:
Martínez-García E;Leopoldo M;Lacivita E;Terrón JA

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探讨药物刺激5-HT 7受体是否调节大鼠三叉神经尾侧核Fos样免疫反应性。5-羟色胺5-HT 7受体被认为参与偏头痛的发病机制,并且有证据表明它通过对感觉传入神经元的作用在外周伤害感受和痛觉过敏中起作用。5-HT 7受体对三叉神经感觉神经元的潜在激活或敏化作用,如可视化的Fos样免疫反应在大鼠三叉神经尾侧核的浅层,使用5-HT 7受体激动剂,LP-211,在脑池内辣椒素的存在和不存在下,分别进行了研究。用5-HT 7受体拮抗剂SB-656104 A表征激动剂作用。雄性Wistar大鼠皮下注射LP-211、SB-656104 A和SB-656104 A + LP-211。然后将它们麻醉并准备接受脑池内注射辣椒素或其载体。对动物进行灌注并取出脑;获得从最后区至CI水平的脑干切片并进行Fos免疫组织化学处理。辣椒素,而不是其车辆诱导Fos样免疫反应在板层I和II的三叉神经核尾侧。用LP-211预处理对Fos样免疫反应性没有影响,但强烈增加了辣椒素产生的反应; SB-656104 A消除了这种影响。有趣的是,辣椒素诱导的Fos样免疫反应性被SB-656104 A预处理消除,从而表明内源性5-HT的参与。数据表明,5-HT 7受体增加脑膜三叉神经血管传入神经的激活和/或脑干中伤害性信息的传递。这种机制可能与偏头痛及其预防性治疗有关。
To explore whether pharmacological stimulation of the 5-HT7 receptor modulates Fos-like immunoreactivity in the trigeminal nucleus caudalis of rats. The serotonin 5-HT7 receptor was proposed to be involved in migraine pathogenesis and evidence suggests it plays a role in peripheral nociception and hyperalgesia through an action on sensory afferent neurons. The potential activating or sensitizing role of 5-HT7 receptors on trigeminal sensory neurons, as visualized by Fos-like immunoreactivity in the superficial layers of the trigeminal nucleus caudalis in rats, was investigated using the 5-HT7 receptor agonist, LP-211, in the absence and the presence of intracisternal capsaicin, respectively. The agonist effect was characterized with the 5-HT7 receptor antagonist, SB-656104A. Male Wistar rats received a subcutaneous injection of LP-211, SB-656104A, and SB-656104A + LP-211. They were then anesthetized and prepared to receive an intracisternal injection of capsaicin or its vehicle. Animals were perfused and brains removed; sections of the brain stem from the area postrema to the CI level were obtained and processed for Fos immunohistochemistry. Capsaicin but not its vehicle induced Fos-like immunoreactivity within laminae I and II of trigeminal nucleus caudalis. Pretreatment with LP-211 had no effect on Fos-like immunoreactivity but strongly increased the response produced by capsaicin; this effect was abolished by SB-656104A. Interestingly, capsaicin-induced Fos-like immunoreactivity was abolished by SB-656104A pretreatment thus suggesting involvement of endogenous 5-HT. Data suggest that 5-HT7 receptors increase activation of meningeal trigeminovascular afferents and/or transmission of nociceptive information in the brain stem. This mechanism could be relevant in migraine and its prophylactic treatment.
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